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Recovery of hypothalamo–pituitary–adrenal axis suppression during treatment with inhaled corticosteroids for childhood asthma

Authors Gangadharan A, McCoy P, Phyo A, McGuigan MP, Dharmaraj P, Ramakrishnan R, McNamara PS, Blair J

Received 1 June 2017

Accepted for publication 14 August 2017

Published 15 December 2017 Volume 2017:10 Pages 317—326

DOI https://doi.org/10.2147/JAA.S142874

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Amrita Dosanjh


Arundoss Gangadharan,1 Paul McCoy,2 Aye Phyo,1 Michael P McGuigan,3 Poonam Dharmaraj,1 Renuka Ramakrishnan,1 Paul S McNamara,2,4 Joanne Blair1

1Department of Endocrinology, 2Department of Respiratory Medicine, Alder Hey Children’s Hospital, Liverpool, 3Department of Paediatrics, Countess of Chester Hospital NHS Foundation Trust, 4Institute in the Park, University of Liverpool, Alder Hey Children’s Hospital, Liverpool, UK

Objective:
To describe recovery of adrenal insufficiency in asthmatic children treated with inhaled corticosteroids (ICS) and cortisol replacement therapy.
Design: Retrospective, observational study.
Patients: A total of 113 patients, 74 male; age 10.4 (3.3–16.5) years; beclomethasone-­equivalent ICS dose, 800 µg, (100–1,000), tested by low dose short Synacthen (tetracosactide) test (LDSST), were studied. Test results were classified by basal and peak cortisol concentration: “normal” (basal >100 nmol/L, peak >500 nmol/L), “suboptimal” (basal >100 nmol/L, peak 350–499 nmol/L), “abnormal” (basal <100 nmol/L and/or peak <350 nmol/L). Patients with suboptimal results received hydrocortisone during periods of stress only, and those with abnormal responses received daily hydrocortisone, increased during periods of stress. A total of 73 patients (68%) had ≥2 LDSSTs over 2.2 years (0.2–7.7).
Measurements: Change in cortisol response to repeat LDSST (movement between diagnostic groups, difference in basal and peak cortisol >15% [2× the inter-assay coefficient of variation]), change in BMI and height standard deviation score (SDS).
Results: Baseline test results were abnormal in 17 patients (15%) and all of them had repeat tests. In 13 patients (76%), test results improved (normal in six, suboptimal in seven) and four (24%) remained abnormal. Baseline tests results were suboptimal in 54 patients (48%), of whom 50 (93%) were retested. Repeat tests were normal in 36 patients (72%), remained suboptimal in 11 (22%), and were abnormal in three (6%). Baseline tests results were normal in 42 patients, of whom six patients (14%) were retested. Results remained normal in three (50%), were suboptimal in two (33%), and abnormal in one (17%). Basal and peak cortisol levels increased by >15% in 33/73 (45%) and 42/73 (57%) patients, respectively, and decreased by >15% in 14/73 (19%) and 7/73 (10%), respectively. There was no significant change in height or BMI SDS.
Conclusion: Recovery of adrenal function is common and occurs during continued ICS and cortisol replacement therapy.

Keywords: HPA axis recovery, adrenal suppression, childhood asthma, inhaled steroids (ICS), LDSST

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